Primer | Published:

Insomnia disorder

Nature Reviews Disease Primers volume 1, Article number: 15026 (2015) | Download Citation

Abstract

Insomnia disorder affects a large proportion of the population on a situational, recurrent or chronic basis and is among the most common complaints in medical practice. The disorder is predominantly characterized by dissatisfaction with sleep duration or quality and difficulties initiating or maintaining sleep, along with substantial distress and impairments of daytime functioning. It can present as the chief complaint or, more often, co-occurs with other medical or psychiatric disorders, such as pain and depression. Persistent insomnia has been linked with adverse long-term health outcomes, including diminished quality of life and physical and psychological morbidity. Despite its high prevalence and burden, the aetiology and pathophysiology of insomnia is poorly understood. In the past decade, important changes in classification and diagnostic paradigms have instigated a move from a purely symptom-based conceptualization to the recognition of insomnia as a disorder in its own right. These changes have been paralleled by key advances in therapy, with generic pharmacological and psychological interventions being increasingly replaced by approaches that have sleep-specific and insomnia-specific therapeutic targets. Psychological and pharmacological therapies effectively reduce the time it takes to fall asleep and the time spent awake after sleep onset, and produce a modest increase in total sleep time; these are outcomes that correlate with improvements in daytime functioning. Despite this progress, several challenges remain, including the need to improve our knowledge of the mechanisms that underlie insomnia and to develop more cost-effective, efficient and accessible therapies.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition: DSM-5 (American Psychiatric Association, 2013).

  2. 2.

    American Academy of Sleep Medicine. International Classification of Sleep Disorders 3rd edn (American Academy of Sleep Medicine, 2014).

  3. 3.

    et al. Monthly fluctuations of insomnia symptoms in a population-based sample. Sleep 37, 319–326 (2014).

  4. 4.

    , , & An international survey of sleeping problems in the general population. Curr. Med. Res. Opin. 24, 307–317 (2008).

  5. 5.

    , & Insomnia, trouble sleeping, and complementary and alternative medicine: analysis of the 2002 National Health Interview Survey data. Arch. Intern. Med. 166, 1775–1782 (2006).

  6. 6.

    et al. Sleep problems, comorbid mental disorders, and role functioning in the National Comorbidity Survey Replication. Biol. Psychiatry 60, 1364–1371 (2006).

  7. 7.

    , , , & Association of insomnia severity and comorbid medical and psychiatric disorders in a health plan-based sample: insomnia severity and comorbidities. Sleep Med. 11, 69–74 (2010).

  8. 8.

    , , , & Prevalence and polysomnographic correlates of insomnia comorbid with medical disorders. Sleep 34, 859–867 (2011).

  9. 9.

    Insomnia. JAMA 309, 706–716 (2013).

  10. 10.

    & Chronic insomnia. Lancet 379, 1129–1141 (2012).

  11. 11.

    & Epidemiological and clinical relevance of insomnia diagnosis algorithms according to the DSM-IV and the International Classification of Sleep Disorders (ICSD). Sleep Med. 10, 952–960 (2009).

  12. 12.

    et al. Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, tenth revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders. Biol. Psychiatry 69, 592–600 (2011).

  13. 13.

    Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med. Rev. 6, 97–111 (2002).

  14. 14.

    et al. Prevalence of insomnia and its treatment in Canada. Can. J. Psychiatry. 56, 540–548 (2011).

  15. 15.

    , , & Moderators and mediators of the relationship between stress and insomnia: stressor chronicity, cognitive intrusion, and coping. Sleep 37, 1199–1208 (2014).

  16. 16.

    et al. Incidence and risk factors of insomnia in a population-based sample. Sleep 32, 1027–1037 (2009).

  17. 17.

    , , , & Epidemiology of insomnia: a longitudinal study in a UK population. Sleep 30, 274–280 (2007).

  18. 18.

    , & The nature of stable insomnia phenotypes. Sleep 38, 127–138 (2015).

  19. 19.

    et al. The natural history of insomnia: a population-based 3-year longitudinal study. Arch. Intern. Med. 169, 447–453 (2009). This study reports on the natural history of insomnia symptoms and syndrome over a period of 3 years in a population-based sample.

  20. 20.

    , , , & Insomnia in men — a 10-year prospective population based study. Sleep 24, 425–430 (2001).

  21. 21.

    , , , & The daytime impact of DSM-5 insomnia disorder: comparative analysis of insomnia subtypes from the Great British Sleep Survey. J. Clin. Psychiatry 73, e1478–e1484 (2012).

  22. 22.

    , & The burden of insomnia on individual function and healthcare consumption in Australia. Aust. N. Z. J. Public Health 36, 462–468 (2012).

  23. 23.

    , , & Epidemiology of DSM-IV insomnia in adolescence: lifetime prevalence, chronicity, and an emergent gender difference. Pediatrics 117, e247–e256 (2006).

  24. 24.

    , , & Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep 27, 1255–1273 (2004).

  25. 25.

    et al. Sleep symptoms, race/ethnicity, and socioeconomic position. J. Clin. Sleep Med. 9, 897–905 (2013).

  26. 26.

    , & Ethnic differences in symptoms of insomnia among adolescents. Sleep 29, 359–365 (2006).

  27. 27.

    , , & Sleep disorders in African Americans and Caucasian Americans: a meta-analysis. Behav. Sleep Med. 8, 246–259 (2010).

  28. 28.

    , , & Associations between seasonal variations in day length (photoperiod), sleep timing, sleep quality and mood: a comparison between Ghana (5°) and Norway (69°). J. Sleep Res. 21, 176–184 (2012).

  29. 29.

    , & Is there a negative impact of winter on mental distress and sleeping problems in the subarctic: the Tromsø Study. BMC Psychiatry 12, 225 (2012).

  30. 30.

    , , & Seasonal variations in sleep problems at latitude 63°–65° in Norway: the Nord-Trondelag Health Study, 1995–1997. Am. J. Epidemiol. 174, 147–153 (2011).

  31. 31.

    , & Sleep of Andean high altitude natives. Eur. J. Appl. Physiol. Occup. Physiol. 64, 178–181 (1992).

  32. 32.

    et al. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J. Affect. Disord. 135, 10–19 (2011).

  33. 33.

    , , & Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol. Psychiatry 39, 411–418 (1996).

  34. 34.

    , & Stress and sleep reactivity: a prospective investigation of the stress–diathesis model of insomnia. Sleep 37, 1295–1304 (2014).

  35. 35.

    , & Trouble sleeping and anxiety/depression in childhood. Psychiatry Res. 94, 93–102 (2000).

  36. 36.

    , & The association of insomnia with anxiety disorders and depression: exploration of the direction of risk. J. Psychiatr. Res. 40, 700–708 (2006).

  37. 37.

    , & Meta-analysis of sleep disturbance and suicidal thoughts and behaviors. J. Clin. Psychiatry 73, e1160–e1167 (2012).

  38. 38.

    , , , & Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep 32, 491–497 (2009).

  39. 39.

    et al. Insomnia with objective short sleep duration and incident hypertension: the Penn State Cohort. Hypertension 60, 929–935 (2012).

  40. 40.

    et al. Persistent insomnia is associated with mortality risk. Am. J. Med. 128, 268–275.e2 (2015).

  41. 41.

    , , & Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med. Rev. 17, 241–254 (2013). This paper reviews the data that suggest the specific insomnia phenotype of ‘objectively measured short sleep’ is an important determinant of insomnia morbidity.

  42. 42.

    et al. Insomnia, comorbidity, and risk of injury among insured Americans: results from the America Insomnia Survey. Sleep 35, 825–834 (2012).

  43. 43.

    , , & Risk factors for major injurious falls among the home-dwelling elderly by functional abilities. A prospective population-based study. Gerontology 44, 232–238 (1998).

  44. 44.

    et al. Insomnia and hypnotic use, recorded in the minimum data set, as predictors of falls and hip fractures in Michigan nursing homes. J. Am. Geriatr. Soc. 53, 955–962 (2005).

  45. 45.

    et al. Sleep disturbances and risk of falls in older community-dwelling men: the outcomes of Sleep Disorders in Older Men (MrOS Sleep) Study. J. Am. Geriatr. Soc. 62, 299–305 (2014).

  46. 46.

    Insomnia, psychiatric disorders, and the transdiagnostic perspective. Curr. Dir. Psychol. Sci. 17, 299–303 (2008).

  47. 47.

    , & The direct and indirect costs of untreated insomnia in adults in the United States. Sleep 30, 263–273 (2007).

  48. 48.

    et al. Days-out-of-role associated with insomnia and comorbid conditions in the America Insomnia Survey. Biol. Psychiatry 70, 1063–1073 (2011). This study highlights some evidence for the impact of insomnia on QOL with regard to disability outcomes in representative patients.

  49. 49.

    & Societal costs of insomnia. Sleep Med. Rev. 14, 379–389 (2010).

  50. 50.

    et al. Insomnia and its relationship to health-care utilization, work absenteeism, productivity and accidents. Sleep Med. 10, 427–438 (2009).

  51. 51.

    , & A behavioral perspective on insomnia treatment. Psychiatr. Clin. North Am. 10, 541–553 (1987). This paper outlines a conceptual model for the evolution of insomnia, distinguishing the role of predisposing, precipitating and perpetuating factors at different times during the course of insomnia.

  52. 52.

    , & Physiological and medical findings in insomnia: implications for diagnosis and care. Sleep Med. Rev. 18, 111–122 (2014).

  53. 53.

    Insomnia: neurophysiological and neuropsychological approaches. Neuropsychol. Rev. 21, 22–40 (2011).

  54. 54.

    , , , & How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors. Am. J. Psychiatry 158, 848–856 (2001).

  55. 55.

    Mediators and mechanisms of change in psychotherapy research. Annu. Rev. Clin. Psychol. 3, 1–27 (2007).

  56. 56.

    & Sex differences in insomnia: a meta-analysis. Sleep 29, 85–93 (2006).

  57. 57.

    et al. Family studies in insomnia. J. Psychosom. Res. 58, 271–278 (2005).

  58. 58.

    , & Who is predisposed to insomnia: a review of familial aggregation, stress-reactivity, personality and coping style. Sleep Med. Rev. 18, 237–247 (2014). This paper reviews the evidence for the genetics and heritability of insomnia and lays the foundation for future research to identify specific genetic markers of the risk for insomnia disorder.

  59. 59.

    , , & Heritability and mortality risk of insomnia-related symptoms: a genetic epidemiologic study in a population-based twin cohort. Sleep 34, 957–964 (2011).

  60. 60.

    , , & Genetic and environmental influences on insomnia, daytime sleepiness, and obesity in twins. Sleep 29, 645–649 (2006).

  61. 61.

    , , & Evidence for genetic influences on sleep disturbance and sleep pattern in twins. Sleep 13, 318–335 (1990).

  62. 62.

    et al. PER3 polymorphism predicts sleep structure and waking performance. Curr. Biol. 17, 613–618 (2007).

  63. 63.

    et al. Association between a serotonin transporter length polymorphism and primary insomnia. Sleep 33, 343–347 (2010).

  64. 64.

    et al. Functional characterization of the new human GABAA receptor mutation β3(R192H). Hum. Genet. 111, 154–160 (2002).

  65. 65.

    , , , & Genetic and metabolic characterization of insomnia. PLoS ONE 6, e18455 (2011).

  66. 66.

    et al. A genome-wide association study of sleep habits and insomnia. Am. J. Med. Genet. B Neuropsychiatr. Genet. 162, 439–451 (2013).

  67. 67.

    , & The role of genes in the insomnia phenotype. Sleep Med. Clin. 8, 323–331 (2013).

  68. 68.

    , & The genetics of insomnia — evidence for epigenetic mechanisms? Sleep Med. Rev. 18, 225–235 (2014).

  69. 69.

    et al. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med. Rev. 14, 19–31 (2010). This paper summarizes the evidence regarding the role of hyperarousal in the pathophysiology of insomnia.

  70. 70.

    et al. A community-based study on the association between insomnia and hypothalamic–pituitary–adrenal axis: sex and pubertal influences. J. Clin. Endocrinol. Metab. 99, 2277–2287 (2014).

  71. 71.

    et al. Heart rate and heart rate variability modification in chronic insomnia patients. Behav. Sleep Med. 12, 290–306 (2014).

  72. 72.

    et al. Heart rate and heart rate variability in subjectively reported insomnia. J. Sleep Res. 20, 137–145 (2011).

  73. 73.

    & 24-hour metabolic rate in insomniacs and matched normal sleepers. Sleep 18, 581–588 (1995).

  74. 74.

    , , , & The relationship between insomnia and body temperatures. Sleep Med. Rev. 12, 307–317 (2008).

  75. 75.

    et al. Sleep changes in the disorder of insomnia: a meta-analysis of polysomnographic studies. Sleep Med. Rev. 18, 195–213 (2014).

  76. 76.

    et al. Does REM sleep contribute to subjective wake time in primary insomnia? A comparison of polysomnographic and subjective sleep in 100 patients. J. Sleep Res. 17, 180–190 (2008).

  77. 77.

    et al. Increased EEG sigma and beta power during NREM sleep in primary insomnia. Biol. Psychol. 91, 329–333 (2012).

  78. 78.

    et al. Short-term stability of sleep and heart rate variability in good sleepers and patients with insomnia: for some measures, one night is enough. Sleep 35, 1285–1291 (2012).

  79. 79.

    , , & Beta EEG activity and insomnia. Sleep Med. Rev. 5, 363–374 (2001).

  80. 80.

    , , , & MSLT in primary insomnia: stability and relation to nocturnal sleep. Sleep 34, 1647–1652 (2011).

  81. 81.

    , & Does physiological hyperarousal enhance error rates among insomnia sufferers? Sleep 36, 1179–1186 (2013).

  82. 82.

    et al. Insomnia with physiological hyperarousal is associated with hypertension. Hypertension 65, 644–650 (2015).

  83. 83.

    et al. Functional neuroimaging evidence for hyperarousal in insomnia. Am. J. Psychiatry 161, 2126–2128 (2004).

  84. 84.

    , & Neural circuitry of stress-induced insomnia in rats. J. Neurosci. 28, 10167–10184 (2008).

  85. 85.

    , & Hypothalamic regulation of sleep and circadian rhythms. Nature 437, 1257–1263 (2005).

  86. 86.

    et al. REM sleep instability — a new pathway for insomnia? Pharmacopsychiatry 45, 167–176 (2012).

  87. 87.

    et al. Neural correlates of working memory performance in primary insomnia. Sleep 36, 1307–1316 (2013).

  88. 88.

    et al. The caudate: a key node in the neuronal network imbalance of insomnia? Brain 137, 610–620 (2014).

  89. 89.

    et al. Insomnia disorder is associated with increased amygdala reactivity to insomnia-related stimuli. Sleep 37, 1907–1917 (2014).

  90. 90.

    , , , & Reduced orbitofrontal and parietal gray matter in chronic insomnia: a voxel-based morphometric study. Biol. Psychiatry 67, 182–185 (2010).

  91. 91.

    , , & Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry. Sleep 37, 1189–1198 (2014).

  92. 92.

    et al. Increased rostral anterior cingulate cortex volume in chronic primary insomnia. Sleep 36, 991–998 (2013).

  93. 93.

    et al. Insomnia does not appear to be associated with substantial structural brain changes. Sleep 36, 731–737 (2013).

  94. 94.

    et al. Reduced anterior internal capsule white matter integrity in primary insomnia. Hum. Brain Mapp. 35, 3431–3438 (2014).

  95. 95.

    & Characterization of the hypnotic effects of triazolam microinjections into the medial preoptic area. Life Sci. 50, 1117–1128 (1992).

  96. 96.

    , , , & Sleep state switching. Neuron 68, 1023–1042 (2010).

  97. 97.

    et al. Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS). Sleep 31, 1499–1506 (2008).

  98. 98.

    , & Review of the histamine system and the clinical effects of H1 antagonists: basis for a new model for understanding the effects of insomnia medications. Sleep Med. Rev. 17, 263–272 (2013). This paper presents a model for understanding how the effects of recently developed insomnia agents, which are specific blockers of receptors of wake-promoting systems, differ from the effects of benzodiazepines and non-benzodiazepines.

  99. 99.

    Melatonin in humans. N. Engl. J. Med. 336, 186–195 (1997).

  100. 100.

    Physiology. The perfect hypnotic? Science 340, 36–38 (2013).

  101. 101.

    et al. Risk factors for incident chronic insomnia: a general population prospective study. Sleep Med. 13, 346–353 (2012).

  102. 102.

    et al. Longitudinal study on perfectionism and sleep disturbance. World J. Biol. Psychiatry 11, 476–485 (2010).

  103. 103.

    & Is perfectionism related to pre-existing and future insomnia? A prospective study. Br. J. Clin. Psychol. 46, 119–124 (2007).

  104. 104.

    , & Precipitating factors of insomnia. Behav. Sleep Med. 2, 50–62 (2004).

  105. 105.

    et al. Onset of insomnia: role of life-stress events. Psychosom. Med. 43, 439–451 (1981).

  106. 106.

    , , , & Acute insomnia: current conceptualizations and future directions. Sleep Med. Rev. 16, 5–14 (2012).

  107. 107.

    , & in Case Studies in Insomnia (ed. Hauri, P. J.) 19–28 (Plenum Publishing Corporation, 1991).

  108. 108.

    , , & Distinguishing rumination from worry in clinical insomnia. Behav. Res. Ther. 48, 540–546 (2010).

  109. 109.

    , , & Sleep and emotions: a focus on insomnia. Sleep Med. Rev. 14, 227–238 (2010).

  110. 110.

    Insomnia: Psychological Assessment and Management (Guilford Press, 1993).

  111. 111.

    A cognitive model of insomnia. Behav. Res. Ther. 40, 869–893 (2002).

  112. 112.

    , , , & The attention–intention–effort pathway in the development of psychophysiologic insomnia: a theoretical review. Sleep Med. Rev. 10, 215–245 (2006).

  113. 113.

    , , , & Assessing cognitive processes related to insomnia: a review and measurement guide for Harvey's cognitive model for the maintenance of insomnia. Sleep Med. Rev. 23, 46–53 (2015).

  114. 114.

    , & Attention bias for sleep-related stimuli in primary insomnia and delayed sleep phase syndrome using the dot-probe task. Sleep 29, 1420–1427 (2006).

  115. 115.

    , , & High intention to fall asleep causes sleep fragmentation. J. Sleep Res. 23, 295–301 (2014).

  116. 116.

    World Health Organisation. International Statistical Classification of Diseases and Related Health Problems 10th revision. WHO , (2015).

  117. 117.

    & Insomnia with short sleep duration: nosological, diagnostic, and treatment implications. Sleep Med. Clin. 8, 309–322 (2013).

  118. 118.

    , , , & Clinical guideline for the evaluation and management of chronic insomnia in adults. J. Clin. Sleep Med. 4, 487–504 (2008). This paper provides guidelines for the assessment and treatment of insomnia in clinical settings.

  119. 119.

    , , , & Recommendations for a standard research assessment of insomnia. Sleep 29, 1155–1173 (2006). This paper provides guidelines for the assessment of insomnia in research settings.

  120. 120.

    et al. Practice parameters for the indications for polysomnography and related procedures: an update for 2005. Sleep 28, 499–521 (2005).

  121. 121.

    et al. The consensus sleep diary: standardizing prospective sleep self-monitoring. Sleep 35, 287–302 (2012).

  122. 122.

    , & Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2, 297–307 (2001).

  123. 123.

    , , Bé & The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep 34, 601–608 (2011). This paper describes critical cut-off scores for insomnia severity and indications for clinical improvement in treatment.

  124. 124.

    , , , & The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 28, 193–213 (1989).

  125. 125.

    , , , & Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA 281, 991–999 (1999).

  126. 126.

    , & Comorbidity between sleep apnea and insomnia. Sleep Med. Rev. 13, 287–293 (2009).

  127. 127.

    & The treatment of insomnia through mass media, the results of a televised behavioral training programme. Soc. Sci. Med. 45, 1223–1229 (1997).

  128. 128.

    , , , & Vulnerability to stress-related sleep disturbance and hyperarousal. Sleep 27, 285–291 (2004).

  129. 129.

    & Investigating safety behaviours in insomnia: the development of the Sleep-Related Behaviours Questionnaire (SRBQ). Behav. Change 21, 26–36 (2004).

  130. 130.

    , & Improving sleep with mindfulness and acceptance: a metacognitive model of insomnia. Behav. Res. Ther. 50, 651–660 (2012).

  131. 131.

    et al. Mindfulness: a proposed operational definition. Clin. Psychol. Sci. Pract. 11, 230–241 (2004).

  132. 132.

    , & Acceptance and Commitment Therapy, Second Edition: The Process and Practice of Mindful Change (Guilford Press, 2011).

  133. 133.

    et al. Quality of life improvements after acceptance and commitment therapy in nonresponders to cognitive behavioral therapy for primary insomnia. Psychother. Psychosom. 83, 371–373 (2014).

  134. 134.

    National Institues of Health. National Institutes of Health state of the science conference statement on manifestations and management of chronic insomnia in adults, June 13–15, 2005. Sleep 28, 1049–1057 (2005). This consensus paper summarizes the state of evidence on therapies for insomnia.

  135. 135.

    , & Treatment of chronic insomnia by restriction of time in bed. Sleep 10, 45–56 (1987).

  136. 136.

    et al. The evidence base of sleep restriction therapy for treating insomnia disorder. Sleep Med. Rev. 18, 415–424 (2014).

  137. 137.

    et al. Psychological and behavioral treatment of insomnia: update of the recent evidence. Sleep 29, 1398–1414 (2006). This paper summarizes the evidence supporting the efficacy of psychological and behavioural therapies for insomnia.

  138. 138.

    & Insomnia: A Clinical Guide to Assessment and Treatment (Kluwer Academic/Plenum Publishers, 2003).

  139. 139.

    A cognitive theory and therapy for chronic insomnia. J. Cogn. Psychother. 19, 41–59 (2005).

  140. 140.

    et al. Comparative efficacy of behavior therapy, cognitive therapy, and cognitive behavior therapy for chronic insomnia: a randomized controlled trial. J. Consult. Clin. Psychol. 82, 670–683 (2014).

  141. 141.

    & Overcoming Insomnia: A Cognitive–Behavioral Therapy Approach, Therapist Guide 2nd edn (Oxford University Press, 2014).

  142. 142.

    , , & Is a video-based cognitive behavioral therapy for insomnia as efficacious as a professionally administered treatment in breast cancer? Results of a randomized controlled trial. Sleep 37, 1305–1314 (2014).

  143. 143.

    et al. Efficacy of an Internet-based behavioral intervention for adults with insomnia. Arch. Gen. Psychiatry 66, 692–698 (2009).

  144. 144.

    et al. A randomized, placebo-controlled trial of online cognitive behavioral therapy for chronic insomnia disorder delivered via an automated media-rich web application. Sleep 35, 769–781 (2012).

  145. 145.

    Randomized study on the efficacy of cognitive–behavioral therapy for insomnia secondary to breast cancer, part I: sleep and psychological effects. J. Clin. Oncol. 23, 6083–6096 (2005).

  146. 146.

    , , & Behavioral insomnia therapy for fibromyalgia patients: a randomized clinical trial. Arch. Intern. Med. 165, 2527–2535 (2005).

  147. 147.

    et al. Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia. Sleep 31, 489–495 (2008).

  148. 148.

    , , & Evidence-based psychological treatments for insomnia in older adults. Psychol. Aging 22, 18–27 (2007).

  149. 149.

    et al. Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder. Sleep 37, 229–237 (2014).

  150. 150.

    , , & Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABAA receptors supports an allosteric model of modulation. Br. J. Pharmacol. 145, 894–906 (2005).

  151. 151.

    Basic and Clinical Pharmacology (McGraw-Hill Medical, 2009).

  152. 152.

    A compendium of placebo-controlled trials of the risks/benefits of pharmacological treatments for insomnia: the empirical basis for U. S. clinical practice. Sleep Med. Rev. 13, 265–274 (2009).

  153. 153.

    et al. Efficacy and safety of doxepin 1 mg and 3 mg in a 12-week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia. Sleep 33, 1553–1561 (2010).

  154. 154.

    et al. Efficacy and safety of doxepin 3 and 6 mg in a 35-day sleep laboratory trial in adults with chronic primary insomnia. Sleep 34, 1433–1442 (2011).

  155. 155.

    , & Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea. Sleep Breath. 11, 159–164 (2007).

  156. 156.

    , , & The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease. Sleep Breath. 13, 79–84 (2009).

  157. 157.

    , , & Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries. Eur. J. Clin. Pharmacol. 69, 1–10 (2013).

  158. 158.

    et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J. Psychopharmacol. 24, 1577–1601 (2010).

  159. 159.

    , & Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS ONE 8, e63773 (2013).

  160. 160.

    et al. The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J. Gen. Intern. Med. 20, 1151–1158 (2005).

  161. 161.

    et al. Suvorexant in patients with insomnia: results from two 3-month randomized controlled clinical trials. Biol. Psychiatry (2014). This paper reports the results of the pivotal trials for suvorexant, the first in a new class of medications that have therapeutic effects in insomnia by blocking orexin receptors.

  162. 162.

    et al. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet Neurol. 13, 461–471 (2014).

  163. 163.

    et al. Insomnia related to dysthymia: polysomnographic and psychometric comparison with normal controls and acute therapeutic trials with trazodone. Neuropsychobiology 44, 139–149 (2001).

  164. 164.

    et al. Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. Prog. Neuropsychopharmacol. Biol. Psychiatry 26, 249–260 (2002).

  165. 165.

    , & Cognitive, psychomotor and polysomnographic effects of trazodone in primary insomniacs. J. Sleep Res. 20, 552–558 (2011).

  166. 166.

    et al. Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia. Pharmacopsychiatry 29, 187–192 (1996).

  167. 167.

    et al. Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study. J. Clin. Psychiatry 62, 453–463 (2001).

  168. 168.

    et al. The sleep-improving effects of doxepin are paralleled by a normalized plasma cortisol secretion in primary insomnia. A placebo-controlled, double-blind, randomized, cross-over study followed by an open treatment over 3 weeks. Psychopharmacology (Berl.). 170, 423–428 (2003).

  169. 169.

    & The use of prazosin for the treatment of trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol. Psychiatry 61, 925–927 (2007).

  170. 170.

    et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol. Psychiatry 61, 928–934 (2007).

  171. 171.

    et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am. J. Psychiatry 160, 371–373 (2003).

  172. 172.

    et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol. Psychiatry 63, 629–632 (2008).

  173. 173.

    & Gabapentin: pharmacology and its use in pain management. Anaesthesia 57, 451–462 (2002).

  174. 174.

    Pregabalin: its pharmacology and use in pain management. Anesth. Analg. 105, 1805–1815 (2007).

  175. 175.

    et al. A randomized double-blind pilot trial of gabapentin versus placebo to treat alcohol dependence and comorbid insomnia. Alcohol. Clin. Exp. Res. 32, 1429–1438 (2008).

  176. 176.

    & Effects of pregabalin on sleep in generalized anxiety disorder. Int. J. Neuropsychopharmacol. 16, 925–936 (2013).

  177. 177.

    , & Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am. J. Psychiatry 151, 1172–1180 (1994).

  178. 178.

    et al. Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy. JAMA 278, 2170–2177 (1997).

  179. 179.

    et al. Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. Am. J. Psychiatry 159, 5–11 (2002).

  180. 180.

    et al. Cognitive behavioral therapy versus zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial. JAMA 295, 2851–2858 (2006).

  181. 181.

    , , & Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch. Intern. Med. 164, 1888–1896 (2004).

  182. 182.

    et al. Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial. JAMA 301, 2005–2015 (2009). This paper reports on the comparative short-term and long-term effects of cognitive–behavioural therapies used alone and in combination with medication.

  183. 183.

    et al. Psychological and health-related quality of life factors associated with insomnia in a population-based sample. J. Psychosom. Res. 63, 157–166 (2007).

  184. 184.

    et al. Chronic insomnia, quality-of-life, and utility scores: comparison with good sleepers in a cross-sectional international survey. Sleep Med. 13, 43–51 (2012).

  185. 185.

    et al. Insomnia and the performance of US workers: results from the America Insomnia Survey. Sleep 34, 1161–1171 (2011).

  186. 186.

    , & Professional correlates of insomnia. Sleep 29, 171–178 (2006).

  187. 187.

    & The relationship between insomnia and health-related quality of life in patients with chronic illness. J. Fam. Pract. 51, 229–235 (2002).

  188. 188.

    & Insomnia and depressive symptoms in patients with Parkinson's disease. Relationship to health-related quality of life. An interview study of patients living at home. Arch. Gerontol. Geriatr. 32, 23–33 (2001).

  189. 189.

    & Disrupted sleep patterns and daily functioning in patients with chronic pain. Pain Res. Manag. 7, 75–79 (2002).

  190. 190.

    et al. Anxiety disorders in cancer patients: their nature, associations, and relation to quality of life. J. Clin. Oncol. 20, 3137–3148 (2002).

  191. 191.

    , & Impact of insomnia on future functioning of adolescents. J. Psychosom. Res. 53, 561–569 (2002).

  192. 192.

    et al. Zopiclone, sleep and health-related quality of life. Hum. Psychopharmacol. Clin. Exp. 9, 245–251 (1994).

  193. 193.

    et al. Nightly treatment of primary insomnia with eszopiclone for six months: effect on sleep, quality of life, and work limitations. Sleep 30, 959–968 (2007). This study is one of the few to assess the effect of treating chronic insomnia on QOL and work-related outcomes.

  194. 194.

    , & Health-related quality of life in patients with insomnia treated with zopiclone. Pharmacoeconomics 10, 39–44 (1996).

  195. 195.

    , , , & Psychological treatment for insomnia in the regulation of long-term hypnotic drug use. Health Technol. Assess. 8, 1–68 (2004).

  196. 196.

    , , , & Efficacy of cognitive–behavioral therapy for insomnia in women treated for nonmetastatic breast cancer. J. Consult. Clin. Psychol. 71, 189–200 (2003).

  197. 197.

    & in Principles and Practice of Sleep Medicine (eds Krieger, M., Roth, T. & Dement, W. C.) 838–849 (Saunders/Elsevier, 2011).

  198. 198.

    & in Case Studies in Insomnia (ed. Hauri, P.) 1–18 (Plenum Press, 1991).

  199. 199.

    in Principles and Practice of Sleep Medicine (eds Krieger, M., Roth, T. & Dement, W. C.) 838–849 (Saunders/Elsevier, 2011).

Download references

Acknowledgements

Preparation of this manuscript was supported in part by grants to C.M.M. from the US NIH (MH-091053) and the Canadian Institutes of Health Research (MOP42504).

Author information

Affiliations

  1. Université Laval, École de psychologie, 2325 rue des Bibliothèques, Québec City, Québec G1V 0A6, Canada.

    • Charles M. Morin
  2. Henry Ford Hospital Sleep Disorders and Research Center, Detroit, Michigan, USA.

    • Christopher L. Drake
  3. Department of Psychology, University of California, Berkeley, Berkeley, California, USA.

    • Allison G. Harvey
  4. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, USA.

    • Andrew D. Krystal
  5. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.

    • Rachel Manber
  6. Department of Clinical Psychology and Psychophysiology/Sleep Medicine, Center for Mental Disorders, University of Freiburg Medical Center, Freiburg, Germany.

    • Dieter Riemann
    •  & Kai Spiegelhalder

Authors

  1. Search for Charles M. Morin in:

  2. Search for Christopher L. Drake in:

  3. Search for Allison G. Harvey in:

  4. Search for Andrew D. Krystal in:

  5. Search for Rachel Manber in:

  6. Search for Dieter Riemann in:

  7. Search for Kai Spiegelhalder in:

Contributions

Introduction (C.M.M.); Epidemiology (C.L.D.); Mechanisms/pathophysiology (D.R. and K.S.); Diagnosis, screening and prevention (A.G.H. and R.M.); Management (A.D.K. and C.M.M.); Quality of life (C.L.D.); Outlook (C.M.M.); Overview of Primer (C.M.M.).

Competing interests

C.M.M. has served as a consultant for Novartis, Merck and Valeant, has received research contracts from Novartis and Merck, and research grants from the National Institute of Mental Health and the Canadian Institutes of Health Research. C.L.D. has received grants and/or research support from the US NIH, IntelClinic, Merck, Pernix and Teva. He has also served as a consultant for Jazz, Teva and Merck. A.D.K. has received grants and/or research support from the NIH, Teva, Eisai, Sunovion, NeoSync, Brainsway, Janssen, ANS St. Jude and Novartis. He has also served as a consultant for Abbott, Astellas, AstraZeneca, Attentiv, Bristol-Myers Squibb, Teva, Eisai, Eli Lilly, Jazz, Janssen, Merck, Neurocrine, Novartis, Otsuka, Palladin, Pernix, Pfizer, Lundbeck, Roche, Somnus, Sunovion, Somaxon and Vantia. D.R. has served as a consultant for AbbVie. He is also a board member of the Freiburg Educational Institute for Behavioural Therapy (a non-profit institution) and receives honoraria for teaching and supervising psychologists in training to become certified psychotherapists. A.G.H., R.M. and K.S. declare no competing interests.

Corresponding author

Correspondence to Charles M. Morin.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrdp.2015.26

Further reading

  • Biological and clinical insights from genetics of insomnia symptoms

    • Jacqueline M. Lane
    • , Samuel E. Jones
    • , Hassan S. Dashti
    • , Andrew R. Wood
    • , Krishna G. Aragam
    • , Vincent T. van Hees
    • , Linn B. Strand
    • , Bendik S. Winsvold
    • , Heming Wang
    • , Jack Bowden
    • , Yanwei Song
    • , Krunal Patel
    • , Simon G. Anderson
    • , Robin N. Beaumont
    • , David A. Bechtold
    • , Brian E. Cade
    • , Mary Haas
    • , Sekar Kathiresan
    • , Max A. Little
    • , Annemarie I. Luik
    • , Andrew S. Loudon
    • , Shaun Purcell
    • , Rebecca C. Richmond
    • , Frank A. J. L. Scheer
    • , Barbara Schormair
    • , Jessica Tyrrell
    • , John W. Winkelman
    • , Juliane Winkelmann
    • , Kristian Hveem
    • , Chen Zhao
    • , Jonas B. Nielsen
    • , Cristen J. Willer
    • , Susan Redline
    • , Kai Spiegelhalder
    • , Simon D. Kyle
    • , David W. Ray
    • , John-Anker Zwart
    • , Ben Brumpton
    • , Timothy M. Frayling
    • , Deborah A. Lawlor
    • , Martin K. Rutter
    • , Michael N. Weedon
    •  & Richa Saxena

    Nature Genetics (2019)

  • Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways

    • Philip R. Jansen
    • , Kyoko Watanabe
    • , Sven Stringer
    • , Nathan Skene
    • , Julien Bryois
    • , Anke R. Hammerschlag
    • , Christiaan A. de Leeuw
    • , Jeroen S. Benjamins
    • , Ana B. Muñoz-Manchado
    • , Mats Nagel
    • , Jeanne E. Savage
    • , Henning Tiemeier
    • , Tonya White
    • , Joyce Y. Tung
    • , David A. Hinds
    • , Vladimir Vacic
    • , Xin Wang
    • , Patrick F. Sullivan
    • , Sophie van der Sluis
    • , Tinca J. C. Polderman
    • , August B. Smit
    • , Jens Hjerling-Leffler
    • , Eus J. W. Van Someren
    •  & Danielle Posthuma

    Nature Genetics (2019)

  • Genome-wide analysis of insomnia disorder

    • Murray B. Stein
    • , Michael J. McCarthy
    • , Chia-Yen Chen
    • , Sonia Jain
    • , Joel Gelernter
    • , Feng He
    • , Steven G. Heeringa
    • , Ronald C. Kessler
    • , Matthew K. Nock
    • , Stephan Ripke
    • , Xiaoying Sun
    • , Gary H. Wynn
    • , Jordan W. Smoller
    •  & Robert J. Ursano

    Molecular Psychiatry (2018)

  • Effects of digital Cognitive Behavioural Therapy for Insomnia on cognitive function: study protocol for a randomised controlled trial

    • Simon D. Kyle
    • , Madeleine E. D. Hurry
    • , Richard Emsley
    • , Annemarie I. Luik
    • , Ximena Omlin
    • , Kai Spiegelhalder
    • , Colin A. Espie
    •  & Claire E. Sexton

    Trials (2017)

  • Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits

    • Anke R Hammerschlag
    • , Sven Stringer
    • , Christiaan A de Leeuw
    • , Suzanne Sniekers
    • , Erdogan Taskesen
    • , Kyoko Watanabe
    • , Tessa F Blanken
    • , Kim Dekker
    • , Bart H W te Lindert
    • , Rick Wassing
    • , Ingileif Jonsdottir
    • , Gudmar Thorleifsson
    • , Hreinn Stefansson
    • , Thorarinn Gislason
    • , Klaus Berger
    • , Barbara Schormair
    • , Juergen Wellmann
    • , Juliane Winkelmann
    • , Kari Stefansson
    • , Konrad Oexle
    • , Eus J W Van Someren
    •  & Danielle Posthuma

    Nature Genetics (2017)